Pharmaceutical systematics: Description and preliminary investigation of an alternative method for structuring drug information

Objectives: To identify the 30 most common adverse drug events or reactions (ADE/ADRs) within the top 200 medications: (1) by raw incidence, (2) weighted by prescription volume, (3) and weighted by retail dollars. Methods: The Pharmacy Times Top 200 Medications (as ranked by prescription volume) was utilized to identify the top 200 medications in 2008. The ADE/ADRs for each medication were obtained from Facts and Comparisons, Micromedex, and Lexi-Comp and entered into a database. These ADE/ADRs were compiled and summed, identifying the number of times each appeared. These then were ranked to identify the 30 most common ADE/ADRs. The actual prescription volume and total retail dollars for each medication were obtained and listed next to each medication's ADE/ADR. The incidence of each ADE/ADR then was weighted by actual prescription volume and retail dollars to determine the top 30 most common ADE/ADRs. Results: Initial evaluation resulted in 9829 individual ADE/ADRs and summed into 1477 distinct ADE/ADRs, after adjusting for interchangeable terminology. Examples of the 30 most common ADE/ADRs (raw incidence) included: dizziness/vertigo, headache, nausea, vomiting, and diarrhea/loose stools. The list remained the same after weighting by actual prescription volume. After weighting by retail dollars, the order of ADE/ADRs changed slightly. Conclusion: Knowledge of ADE/ADRs is important for pharmacists in all healthcare settings. Consolidating ADE/ADRs for medications may enable pharmacists to recall the most common side effects and aid in earlier identification of ADE/ADRs, which may positively impact patient safety across practice settings. Type: Original Researc

Pharmaceutical Systematics: Description and Preliminary Investigation of an Alternative Method for Structuring Drug Information

Objectives: To identify the 30 most common adverse drug events or reactions (ADE/ADRs) within the top 200 medications: (1) by raw incidence, (2) weighted by prescription volume, (3) and weighted by retail dollars. Methods: The Pharmacy Times Top 200 Medications (as ranked by prescription volume) was utilized to identify the top 200 medications in 2008. The ADE/ADRs for each medication were obtained from Facts and Comparisons, Micromedex, and Lexi-Comp and entered into a database. These ADE/ADRs were compiled and summed, identifying the number of times each appeared. These then were ranked to identify the 30 most common ADE/ADRs. The actual prescription volume and total retail dollars for each medication were obtained and listed next to each medication’s ADE/ADR. The incidence of each ADE/ADR then was weighted by actual prescription volume and retail dollars to determine the top 30 most common ADE/ADRs. Results: Initial evaluation resulted in 9829 individual ADE/ADRs and summed into 1477 distinct ADE/ADRs, after adjusting for interchangeable terminology. Examples of the 30 most common ADE/ADRs (raw incidence) included: dizziness/vertigo, headache, nausea, vomiting, and diarrhea/loose stools. The list remained the same after weighting by actual prescription volume. After weighting by retail dollars, the order of ADE/ADRs changed slightly. Conclusion: Knowledge of ADE/ADRs is important for pharmacists in all healthcare settings. Consolidating ADE/ADRs for medications may enable pharmacists to recall the most common side effects and aid in earlier identification of ADE/ADRs, which may positively impact patient safety across practice setting

Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection

<div><p>Dengue virus (DV) infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR) 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP) reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6^-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection.</p></div

The KELT Follow-up Network and Transit False-positive Catalog: Pre-vetted False Positives for TESS

The Kilodegree Extremely Little Telescope (KELT) project has been conducting a photometric survey for transiting planets orbiting bright stars for over ten years. The KELT images have a pixel scale of ~23"/pixel---very similar to that of NASA's Transiting Exoplanet Survey Satellite (TESS)---as well as a large point spread function, and the KELT reduction pipeline uses a weighted photometric aperture with radius 3'. At this angular scale, multiple stars are typically blended in the photometric apertures. In order to identify false positives and confirm transiting exoplanets, we have assembled a follow-up network (KELT-FUN) to conduct imaging with higher spatial resolution, cadence, and photometric precision than the KELT telescopes, as well as spectroscopic observations of the candidate host stars. The KELT-FUN team has followed-up over 1,600 planet candidates since 2011, resulting in more than 20 planet discoveries. Excluding ~450 false alarms of non-astrophysical origin (i.e., instrumental noise or systematics), we present an all-sky catalog of the 1,128 bright stars (6<V<10) that show transit-like features in the KELT light curves, but which were subsequently determined to be astrophysical false positives (FPs) after photometric and/or spectroscopic follow-up observations. The KELT-FUN team continues to pursue KELT and other planet candidates and will eventually follow up certain classes of TESS candidates. The KELT FP catalog will help minimize the duplication of follow-up observations by current and future transit surveys such as TESS.Comment: Accepted for publication in AJ, 21 pages, 12 figures, 7 table